The work outlined in this proposal is in response to a Request for Applications entitled "Biomedical and Behavioral Research on Alcohol and Youth". Despite the fact that alcohol use typically begins in adolescent or even younger youth, basic research examining the ontogeny of ethanol sensitivity in laboratory animals is relatively sparse and what data are available are surprisingly inconsistent. The work outlined in this proposal is designed as a straight-forward and systematic examination of the ontogeny of ethanol sensitivity, using well-established procedures used in developmental psychopharmacology and with consideration for the special challenges in working with ethanol. Animals of a variety of ages will be examined, including the periadolescent period, an age that we previously have shown to be associated with a variety of age-specific behavioral propensities, including an altered psychopharmacological sensitivity to a variety of drugs. The specific aims of this work are to characterize systematically the ontogeny of ethanol responsiveness in terms of acute ethanol sensitivity and with respect to the development of acute and chronic tolerance to ethanol. To accomplish these aims, three series of experiments are proposed. Experimental Series 1 will examine the ontogeny of acute ethanol sensitivity using a variety of response measures, including assessment of ethanol-induced hypothermia and suppression of startle as well as ethanol-induced alterations in locomotion and in swim speed; dose-response relationships will be systematically assessed, and blood and brain alcohol levels will be examined. Experimental Series 2 will assess the ontogeny of acute ethanol tolerance through the use of linear regression analyses of data on blood and brain alcohol levels at the time of recovery of the righting reflex in animals exposed to a variety of hypnotic doses of ethanol. Experimental Series 3 will examine the ontogeny of chronic tolerance to ethanol as well as the impact of early ethanol exposure on the later development of ethanol tolerance in adulthood; tolerance will be assessed in terms of the hypnotic effects of ethanol as well as ethanol-induced alterations in body temperature, startle amplitude and locomotor activity, with alterations in ethanol elimination rates being used as an index of the development of dispositional tolerance. The results of the studies proposed will provide a solid data base of fundamental information regarding the ontogeny of ethanol responsiveness, findings that may be of substantial importance given the early initiation of alcohol use among youth in the United States.